Studies of the formation of the high molecular weight peptides from the C-terminal half of the alpha-chain of fibrinogen have been completed. Data on bovine and human fibrinogen digested by either plasmin or trypsin were collected. The kinetics of all these reactions were analyzed by computer modeling. In general, one bond is cleaved with a faster rate resulting in a 38,000 molecular weight fragment that is trimmed from the C-terminus in several slower steps to a relatively stable product of a 26,000 molecular weight with plasmin and an 18,000 molecular weight with trypsin. The mechanism is distinctly different with the human bovine fibrinogens.